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PubMed2005

Identification of mouse selenomethionine alpha,gamma-elimination enzyme: cystathionine gamma-lyase catalyzes its reaction to generate methylselenol.

The purpose of this study was to identify the seleno-L-methionine (L-SeMet) alpha,gamma-elimination enzyme that catalyzes L-SeMet to generate methylselenol (CH3SeH), a notable intermediate for the metabolism of selenium compounds, in mammalian tissues. The enzyme purified from ICR mouse liver was separated by one-dimensional gel electrophoresis, and the specific band was subjected to in-gel trypsin digestion followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometric analysis. In the peptide mass fingerprinting search, the mass numbers of 14 peptides produced by tryptic digestion of the enzyme were consistent with the theoretical mass numbers calculated from the amino acid sequence of murine cystathionine gamma-lyase (E.C. 4.4.1.1). The peptide sequence tags search was also performed to obtain the amino acid sequence data of five tryptic peptides. These peptides were significantly identical to the partial amino acid sequences of cystathionine gamma-lyase. This enzyme was clearly shown to catalyze the alpha,gamma-elimination reaction of L-cystathionine by the enzymological research. The Km value for the catalysis of L-cystathionine was 0.81 mM and Vmax was 0.0013 unit/mg protein. These results suggested that cystathionine gamma-lyase catalyzes L-SeMet to generate CH3SeH by its alpha,gamma-elimination reaction.

Amino Acid Sequence↗
PubMed2006

A convenient and stereoselective synthesis of (Z)-allyl selenides via Sm/TMSCl system-promoted coupling of Baylis-Hillman adducts with diselenides.

A simple and convenient procedure for stereoselective synthesis of (Z)-allyl selenides has been developed by a one-pot reaction of diselenides with Baylis-Hillman adducts in the presence of samarium metal-trimethylsilyl chloride under mild conditions. Presumably, the diselenides are cleaved by Sm/TMSCl system to form selenide anions, which then undergo S(N)2' substitution of Baylis-Hillman adducts to produce the (Z)-allyl selenides.

Magnetic Resonance Spectroscopy↗
PubMed2001

A prevention strategy for circumventing drug resistance in cancer chemotherapy.

The development of drug resistance is considered to be a major cause for the failure of chemotherapy in a number of types of cancer, including ovarian, breast and lung. Most previous research has focused on approaches to reverse drug resistance once it has arisen, that is, on the use of agents which can make drug-resistant tumors more sensitive to chemotherapy. Unfortunately, this approach has thus far met with only limited clinical success. Because of the prevalence of drug resistance in cases of advanced cancer, there exists an urgent need to develop new approaches to dealing with this problem. We have hypothesized the feasibility of an alternative approach: the use of specific agents to prevent the development of resistance before it arises. Our initial studies to examine this hypothesis have focused on ovarian cancer. We have designed both in vitro and in vivo systems in which resistance develops rapidly after exposure of tumor cells or xenografts to melphalan or cisplatin. Using these systems we have shown that two selenium compounds, selenite and selenomethionine are able to prevent the induction of resistance. Furthermore, inclusion of selenite in a chemotherapeutic protocol can result in a significant enhancement of the efficacy of cisplatin in suppressing the growth of human ovarian tumor xenografts. These results have supported the idea that prevention may be a useful new approach to the problem of drug resistance in cancer chemotherapy.

Animals↗
PubMed1990

DNA damage, repair, and replication in selenite-induced cataract in rat lens.

DNA synthesis was evaluated in vitro by measuring incorporation of 3H-thymidine in rat lens following systemic delivery of a cataractogenic dose of selenite. Among early metabolic changes observed in the lenses of rats receiving a single dose of 30 nmol Na2SeO3/g body weight was a 30% decrease in DNA replication in lens epithelium occurring between 6 and 12 h after administration of the selenite. This change was followed by an 80% increase in replication by 24 h. Thymidine incorporation in DNA remained elevated compared to controls through 96 h. Unscheduled DNA synthesis was found to be approximately 10% of the total DNA formed, but there was a 30% and 70% increase of this putative DNA repair in the lenses from selenite-treated animals at 6 and 24 h after the injection. Using the alkaline unwinding assay, the proportion of single-strand DNA in lenses from selenite-treated animals increased after 24 h. This estimate of DNA damage was greater in lenses after 96 h. Each component of DNA metabolism: damage, repair, and replication, was affected by the occurrence of selenite stress in lens. These changes both preceded and accompanied nuclear cataract formation.

Animals↗
PubMed1984

Effects of dietary protein level and level of feed intake on the apparent bioavailability of selenium for the chick.

Experiments were conducted to determine the effects of dietary protein level and level of feed intake on the apparent bioavailability of Se from Na2SeO3 and selenomethionine (DL-Se-Met) for protection from exudative diathesis (ED) of the Se- and vitamin E-depleted chick. Level of dietary protein (22.5 vs. 16.9%) significantly (P less than .01) affected the incidence of ED at several levels of dietary Se from each source. At each level of Se, the low protein diet resulted in a lower incidence of ED and, thus, an increase in the apparent bioavailability of Se; Se from Na2SeO3 was more available than that from Se-Met. Further experiments were conducted to determine whether the effect of dietary protein level on the incidence of ED was due to effects on growth rate or feed intake. Chicks were fed the high or low protein basal diets at 75% of ad libitum rate of feed consumption. Sodium selenite was added to make Se intakes equivalent, either on a per day or a per unit gain basis, to ad libitum feeding controls receiving the Se-supplemented diets. Results showed that both a low level of dietary protein and a restricted level of feeding markedly reduced the incidence and severity of ED. The activity of Se-dependent glutathione peroxidase (SeGSHpx) in plasma and liver varied inversely with the incidence of ED and was increased by feed restriction. These results suggest that growth rate affects both the clinical and biochemical manifestations of Se-deficiency in the chick. Because both parameters are used to assess the bioavailability of Se in feeds and foods, bioassays in which growth rate is different between test and reference treatments may yield incorrect results.

Animals↗
PubMed2000

[The immunomodulating properties of pharmacological preparations].

According to the analysis of literary data there are immunomodulating properties in the drugs that are used with different purposes: in tranquilizers, neuroleptics, stimulators of central nervous system, nonsteroid antiinflammatory agents, azole group, spasmolytics, sulphur and selenium compounds, blockers of calcic canals and other compounds. During the clinical application of pharmaceutic drugs it is necessary to consider their immunotropic properties as a side effect. Besides, the immunostimulating action of the above-mentioned compounds permits to use them in prophylaxis and treatment of different immunodeficient states.

Adjuvants, Immunologic↗
PubMed2001

[In vivo and in vitro effects of selenium-enriched garlic on growth of human gastric carcinoma cells].

OBJECTIVE: To compare the effects of selenium-enriched garlic (Se-garlic), garlic, Na2SeO3, and garlic + Na2SeO3 on growth of human gastric carcinoma cells. METHODS: In vivo and in vitro assays were carried out in the cultured human gastric carcinoma cell line MGC803 transplanted in the nude mice by cell count, flow cytometry, Western blot and neoplasm volume measurement. RESULTS: The inhibition effect of garlic was similar to that of Se-garlic, but Na2SeO3 was weaker than Se-garlic. Combination of garlic and Na2SeO3 was stronger than Se-garlic. In flow cytometry assay, the proportion of G1 phase was increased after 24 hour treatment of Se-garlic, garlic and Na2SeO3 in the non-synchronized cells. However, the proportion of S phase was increased in the synchronized cells. The proportion of G2 + M phase was increased both in non-synchronized and synchronized cells on treatment with the combination of garlic and Na2SeO3. The amount of Cdk2-CyclinE complex and Cdk4-CyclinD1 complex was decreased in all treated synchronized cells in immunoprecipitation and immunoblot assays. The growth of MGC803 tumor in male Balb/c nude mice was inhibited by administration of 1.67% of Se-garlic (Se 2 micrograms/g) in diet with an inhibition rate of 29.92% in tumor weight. Treatment of either 0.83% of Se-garlic or 1.67% of garlic or 4.38 micrograms/g of Na2SeO3 (Se 2 micrograms/g) could not appreciably inhibit the growth of tumor. Wrapping of a number of monocytes around the tumor was induced in 62.50% of tumors in 0.83% of the Se-garlic group. CONCLUSION: In vitro, Se-garlic is able to inhibit the growth of MGC803 cell through action of garlic. In vivo, Segarlic is able to inhibit growth of MGC803 tumor in nude mice by being better than garlic and selenite.

Animals↗
PubMed2003

[Effects of selenium dioxide on regulatory regions P250 of c-fos gene].

BACKGROUND & OBJECTIVE: This study was designed to investigate the impact of selenium dioxide (SeO2) on regulatory regions P250 of c-fos gene and to seek possible regulation mechanism. METHODS: HeLa cells were transfected with plasmids containing upstream regulating regions of c-fos chloramphenicol acetyl-transferase (CAT). The cells were cultured in various concentration of selenium dioxide. CAT expression in transfected cells was observed. RESULTS: After transfected HeLa cells were exposed to selenium dioxide, CAT expression showed obvious increase, especially in 10 micromol/L and 30 micromol/L selenium dioxide group (P< 0.05). CONCLUSION: Trough affecting regulatory regions P250 of c-fos gene, Selenium dioxide plays biological effect of regulating tumor cells. Selenium dioxide possibly has anti-tumor effects.

Chloramphenicol O-Acetyltransferase↗
PubMed2003

[Effect of selenium dioxide on proliferation, apoptosis, and elomerase activity of human lung cancer cell line in vitro].

BACKGROUND & OBJECTIVE: It was reported that selenium could induce apoptosis of cancer cells; moreover, apoptosis of cancer cells and telomerase activity were closely related to the development of cancer. This study was designed to investigate the effect of selenium dioxide on human pulmonary adenocarcinoma GLC-82 cell to reveal its probable mechanism and the relationship between apoptosis and telomerase activity. METHODS: Methyl thiazolyl tetrazolium(MTT) method was used to determine the growth inhibition rates of lung cancer GLC-82 cells by various concentrations of selenium dioxide at different time. TRAP-PCR-ELISA assay was used to examine the changes of GLC-82 cells treated with selenium dioxide. The cell apoptotic rate was measured by flow cytometry (FCM). DNA ladder was showed by DNA agarose gel electrophoresis. The morphological changes of the cancer cells were examined under light and electron microscope. RESULTS: After being treated with 3, 10, 30 micromol/L selenium dioxide, the proliferation and telomerase activity of GLC-82 cells were markedly inhibited. The growth inhibition rates in GLC-82 cells for 24 hours were 0.7%, 12.8%, and 31.8%; for 72 hours were 15.1%, 51.2%, and 61.1%, respectively. Telomerase activity of GLC-82 cells for 24 hours were 1.173+/-0.029,1.127+/-0.067, and 1.050+/-0.098(P< 0.05); for 48 hours were 1.150+/-0.026, 1.047+/-0.060, and 0.950+/-0.036(P< 0.05), respectively (control group: 1.227+/-0.032 and 1.167+/-0.023, respectively). An apoptosis peak appeared before diploid peak in FCM. Agarose gel electrophoresis showed overt ladder-shape band of cell apoptosis. GLC-82 cells treated by selenium dioxide showed morphological characteristics of apoptotic cells. CONCLUSION: Selenium dioxide could significantly inhibit the growth of lung cancer GLC-82 cells through inducing apoptosis and inhibiting the telomerase activity. Selenium dioxide has strong growth inhibitory effect in a dose-and time-dependent manner.

Apoptosis↗
PubMed1992

Transplacental passage and fetal deposition of mercury after low-level exposure to methylmercury--effect of seleno-L-methionine.

Previous experimental studies on transplacental passage and possible fetotoxicity of methylmercury have almost exclusively used a single dosage or 2-4 repeated doses of mercury on specific days during gestation and often used at relatively high dose levels. In previous studies, selenium supplementation considerably increased the concentration of mercury in the blood of offspring after maternal exposure of rats to methylmercury, whereas whole-body retention and organ deposition of mercury in mice were unaffected. The present study in mice, which involved exposure for 5 weeks to a low dose of methylmercury in the drinking water (1 nmol/ml) before and during pregnancy, demonstrates that mercury is deposited in offspring both in utero and during lactation, and that transplacentally absorbed mercury is not, or only very slowly, excreted. Seleno-L-methionine increased the deposition of mercury in offspring, but the effect was due to slightly higher deposition in the dams. Selenomethionine significantly reduced the kidney deposition of mercury in offspring, whereas liver deposition of mercury was unaffected. These results indicate that interactions between organo-selenium compounds and methylmercury orally administered at low doses is of less importance than previously believed on the basis of experiments with higher doses of selenite injected or supplemented to the diet.

Adolescent↗